NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML.
Animals
Apoptosis
/ genetics
Biomarkers, Tumor
/ genetics
Blast Crisis
/ genetics
CD56 Antigen
/ genetics
Drug Resistance, Neoplasm
Female
Glycolysis
/ genetics
HL-60 Cells
Humans
K562 Cells
Leukemia, Myeloid, Acute
/ genetics
MAP Kinase Signaling System
/ genetics
Male
Mice
Mice, Inbred NOD
Mice, Knockout
Neoplasm Proteins
/ genetics
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
23 05 2019
23 05 2019
Historique:
received:
03
12
2018
accepted:
21
02
2019
pubmed:
1
3
2019
medline:
24
12
2019
entrez:
1
3
2019
Statut:
ppublish
Résumé
Neural cell adhesion molecule 1 (NCAM1; CD56) is expressed in up to 20% of acute myeloid leukemia (AML) patients. NCAM1 is widely used as a marker of minimal residual disease; however, the biological function of NCAM1 in AML remains elusive. In this study, we investigated the impact of NCAM1 expression on leukemogenesis, drug resistance, and its role as a biomarker to guide therapy. Beside t(8;21) leukemia, NCAM1 expression was found in most molecular AML subgroups at highly heterogeneous expression levels. Using complementary genetic strategies, we demonstrated an essential role of NCAM1 in the regulation of cell survival and stress resistance. Perturbation of NCAM1 induced cell death or differentiation and sensitized leukemic blasts toward genotoxic agents in vitro and in vivo. Furthermore, Ncam1 was highly expressed in leukemic progenitor cells in a murine leukemia model, and genetic depletion of
Identifiants
pubmed: 30814062
pii: S0006-4971(20)42538-8
doi: 10.1182/blood-2018-12-889725
doi:
Substances chimiques
Biomarkers, Tumor
0
CD56 Antigen
0
NCAM1 protein, human
0
Ncam1 protein, mouse
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2305-2319Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 by The American Society of Hematology.